Abstract

Given the heterogeneous nature of cultures, tumors, and tissues, the ability to capture, contain, and analyze single cells is important for genomics, proteomics, diagnostics, therapeutics, and surgery. Moreover, for surgical applications in small conduits in the body such as in the cardiovascular system, there is a need for tiny tools that approach the size of the single red blood cells that traverse the blood vessels and capillaries. We describe the fabrication of arrayed or untethered single cell grippers composed of biocompatible and bioresorbable silicon monoxide and silicon dioxide. The energy required to actuate these grippers is derived from the release of residual stress in 3-27 nm thick films, did not require any wires, tethers, or batteries, and resulted in folding angles over 100° with folding radii as small as 765 nm. We developed and applied a finite element model to predict these folding angles. Finally, we demonstrated the capture of live mouse fibroblast cells in an array of grippers and individual red blood cells in untethered grippers which could be released from the substrate to illustrate the potential utility for in vivo operations.

Illustration of single cell gripper fabrication and use on substrates or as untethered tools. (a) Fabrication scheme for creating single cell grippers. The prestressed actuator hinge is a SiO/SiO2 bilayer, while the rigid segments are made of SiO. Upon dissolution of the sacrificial layer, the arms are released and self-actuate to close around cells. An optional thermoresponsive trigger layer can be molded atop the grippers. (b) Illustration of cells captured by single cell microgrippers arrays. (c) Illustration of untethered single cell grippers and red blood cell capture.

Optical images of single cell grippers before and after closing. (a) Optical image of grippers released from the substrate with open arms prior to closing, in sizes ranging from 10 to 50 μm. (b–c) Zoomed optical images of 50 μm grippers (b) prior to release from the substrate and (c) closed tightly after release. (d–e) Optical images of 10 μm grippers (d) open and (e) closed. Scale bars are (a, b, c) 25 μm and (d, e) 10 μm. (f–g) SEM images at different magnifications of closed single cell grippers attached to the substrate. Scale bars are (f) 10 μm and (g) 5 μm.

Characterization of thin film stress and gripper folding angle. (a) Graphs depicting the effect of mismatch strain (left panel) and SiO/SiO2 thickness (right panel) on folding angle for the 70 μm gripper. (b) Graphs depicting the effect of mismatch strain (left panel) and SiO/SiO2 thickness (right panel) on folding angle for the 10 μm gripper. The inset images of a folded gripper with angle measurement in the left panels are optical microscopy images of actual folded grippers for comparison to the modeled gripper folding. The red star on these graphs indicates the experimentally observed folding angle for these experimentally observed grippers. More details of the parameters used to generate the models and graphs are in the .

Single cell microgripper arrays. (a–c) Individual cells captured within the arms of grippers. Since the films are optically transparent, cells captured by the grippers can be readily visualized using optical microscopy. (c, inset) The cell shown is entrapped by a gripper, as evidenced by the square appearance of the cell when viewed from the top, which matches the square shape of the base of the gripper. (d) SEM image of a cell trapped within the arms of a gripper, surrounded by untrapped cells. Scale bars are 10 μm.